title: Telaprevir activity in treatment-naive patients infected hepatitis C virus genotype 4: a randomized trial.
abstract: BACKGROUND
  This partially blinded, randomized, phase 2a C210 study evaluated the antiviral activity of telaprevir-based regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 4 infection.
  
  
  METHODS
  Twenty-four patients received telaprevir 750 mg every 8 hours for 15 days (T; n = 8), telaprevir in combination with pegylated interferon alfa-2a and ribavirin (Peg-IFN/RBV) for 15 days (TPR; n = 8), or Peg-IFN/RBV plus placebo for 15 days (PR; n = 8), followed by Peg-IFN/RBV for 46 or 48 weeks. The primary objective was to assess the effect of telaprevir on HCV RNA levels.
  
  
  RESULTS
  HCV RNA levels decreased slightly with T and PR; TPR produced substantial, rapid declines. On day 15, median reductions in the HCV RNA load from baseline were -0.77, -4.32, and -1.58 log10 IU/mL for T, TPR, and PR, respectively, and 0 patients in the T group, 1 in the TPR group, and 0 in the PR group had undetectable HCV RNA. Five of 8 patients who received telaprevir monotherapy had viral breakthrough within 15 days of treatment. Adverse event incidence was similar across treatments and comparable with the incidences from previous clinical trials. One patient (in T group) had a serious adverse event (considered unrelated to telaprevir) that led to treatment discontinuation.
  
  
  CONCLUSIONS
  Telaprevir with Peg-IFN/RBV had greater activity than Peg-IFN/RBV treatment or telaprevir monotherapy against HCV genotype 4. Telaprevir was generally safe and well tolerated. Further investigation of telaprevir combination therapy in patients with HCV genotype 4 infection is warranted.
authors.affiliation: Service d'Hépato-Gasteroentérologie, Hôpital Pitié-Salpêtrière, Paris, France. ybenhamou@teaser.fr
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Joseph
authors.initials: J
authors.lastname: Moussalli
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.forename: Katrien
authors.initials: K
authors.lastname: De Backer
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Anne
authors.initials: A
authors.lastname: Ghys
authors.forename: Donghan
authors.initials: D
authors.lastname: Luo
authors.forename: Gaston R
authors.initials: GR
authors.lastname: Picchio
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a
keywords: HCV RNA; SVR; Study C210; viral kinetics